The main purpose of this study is to compare progression-free survival for women with hormone receptor positive (HR+), human epidermal growth factor receptor (HER2) negative advanced breastcancer receiving either abemaciclib+fulvestrant or fulvestrant alone. The study will last about 9 months for each participant.

Change from Baseline in Pain and Symptom Burden Assessment Using the Brief Pain Inventory (BPI) [ Time Frame: Baseline, End of Study (up to approximately 31 months) ] [ Designated as safety issue: No ]

Pharmacokinetics (PK): Area Under the Concentration Curve (AUC) of Abemaciclib, Its Metabolites, and Fulvestrant [ Time Frame: Baseline up to Approximately 31 Months ] [ Designated as safety issue: No ]

Time to Worsening of Eastern Cooperative Oncology Group (ECOG) Performance Status [ Time Frame: Baseline up to Approximately 31 Months ] [ Designated as safety issue: No ]

Time to First Skeletal-Related Event (SRE) [ Time Frame: Baseline up to Approximately 31 Months ] [ Designated as safety issue: No ]

Change from Baseline in Health Status Using the EuroQol 5-Dimension 5 Level (EQ-5D 5L) [ Time Frame: Baseline, End of Study (up to approximately 31 months) ] [ Designated as safety issue: No ]

Change from Baseline in Quality of Life Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline, End of Study (up to approximately 31 months) ] [ Designated as safety issue: No ]

Change from Baseline in Quality of Life Using the EORTC QLQ-BR23 (breast) Questionnaire [ Time Frame: Baseline, End of Study (up to approximately 31 months) ] [ Designated as safety issue: No ]

150 milligrams (mg) Abemaciclib given orally once every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections intramuscularly (IM) on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.

Drug: Abemaciclib

Administered Orally

Other Name: LY2835219

Drug: Fulvestrant

Administered IM

Placebo Comparator: Placebo + Fulvestrant

Placebo will be supplied as capsules administered orally every 12 hours in 28 day cycles. 500 mg fulvestrant administered as two 250-mg injections IM on Days 1 and 15 of Cycle 1, then on Day 1 of Cycle 2 and beyond. Participants may continue to receive treatment until discontinuation criteria are met.

Drug: Fulvestrant

Administered IM

Drug: Placebo

Administered Orally

Eligibility

Ages Eligible for Study:

18 Years and older

Genders Eligible for Study:

Female

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria

Have a diagnosis of HR+, HER2- breast cancer

Have either locally advanced disease not amenable to curative treatment by surgery or metastatic disease. In addition, participants must fulfill 1 of the following criteria:

relapsed with radiologic evidence of progression on neoadjuvant or adjuvant endocrine therapy

relapsed with radiologic evidence of progression within 1 year from completion of adjuvant endocrine therapy

relapsed with radiologic evidence of progression more than 1 year from completion of adjuvant endocrine therapy and then subsequently relapsed with radiologic evidence of progression after no more than first-line endocrine therapy (with either an antiestrogen or an aromatase inhibitor) for metastatic disease

presented de novo with locally advanced or metastatic disease and not received any prior endocrine therapy

presented de novo with locally advanced or metastatic disease and then relapsed with radiologic evidence of progression after no more than first-line endocrine therapy (with either an antiestrogen or an aromatase inhibitor)

Have postmenopausal status due to either surgical/natural menopause or ovarian suppression (initiated at least 28 days prior to Day 1 of Cycle 1) with a gonadotropin-releasing hormone (GnRH) agonist such as goserelin

Have a negative serum pregnancy test at baseline (within 14 days prior to randomization) and agree to use medically approved precautions to prevent pregnancy during the study and for 12 weeks following the last dose of abemaciclib if postmenopausal status is due to ovarian suppression with a GnRH agonist

Have either measurable disease or nonmeasurable bone only disease

Have a performance status ≤1 on the ECOG scale

Have discontinued previous therapies for cancer (including specifically, aromatase inhibitors, anti-estrogens, chemotherapy, radiotherapy, and immunotherapy) for at least 21 days for myelosuppressive agents or 14 days for nonmyelosuppressive agents prior to receiving study drug, and recovered from the acute effects of therapy (until the toxicity resolves to either baseline or at least Grade 1) except for residual alopecia or peripheral neuropathy

Exclusion Criteria

Are currently receiving an investigational drug in a clinical trial or participating in any other type of medical research judged not to be scientifically or medically compatible with this study

Have visceral crisis, lymphangitic spread, or leptomeningeal carcinomatosis visceral crisis is not the mere presence of visceral metastases but implies severe organ dysfunction as assessed by symptoms and signs, laboratory studies, and rapid progression of the disease

Have clinical evidence or history of central nervous system metastasis

Have received prior treatment with chemotherapy (except for neoadjuvant/ adjuvant chemotherapy), fulvestrant, everolimus, or any CDK4/6 inhibitor

Have received treatment with a drug that has not received regulatory approval for any indication within 14 or 21 days prior to randomization of study drug for a nonmyelosuppressive or myelosuppressive agent, respectively

Have received recent (within 28 days prior to randomization) yellow fever vaccination

Have had major surgery within 14 days prior to randomization of study drug to allow for post-operative healing of the surgical wound and site(s)

Have a personal history of any of the following conditions: presyncope or syncope of either unexplained or cardiovascular etiology, ventricular tachycardia, ventricular fibrillation, or sudden cardiac arrest

Have inflammatory breast cancer or a history of any other cancer (except nonmelanoma skin cancer or carcinoma in-situ of the cervix), unless in complete remission with no therapy for a minimum of 3 years

Have received an autologous or allogeneic stem-cell transplant

Have active bacterial or fungal infection, or detectable viral infection

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02107703

Contacts

Contact: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or